Metabolic pathway genes linked to AMD and choroidal vasculopathy

Jul 1 2014

By Lucy Piper, Senior medwireNews Reporter

The cholesteryl ester transfer protein (CETP) gene appears to increase susceptibility to neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV), research shows.

Both conditions were significantly associated with the CETP single nucleotide polymorphism (SNP) rs3764261. And these associations occurred independently of two known AMD-associated SNPS, rs800292 on the complement factor H (CFH) gene and rs11200638 on the HtrA serine peptidase 1 (HTRA1) gene.

“Therefore, CETP is an essential gene involved in the development of the 2 diseases”, comment Chi Pui Pang (The Chinese University of Hong Kong) and colleagues.

The researchers genotyped for eight SNPs from six genes involved in high-density lipoprotein (HDL) metabolism together with the two known AMD-associated SNPS in 200 patients with neovascular AMD, 233 with PCV and 275 individuals with healthy eyes.

Patients with AMD or PCV were significantly more likely to carry the minor T allele of CETP rs3764261 than healthy controls, conferring increased risks of 1.89-fold and 1.80-fold, respectively.

There was a significant interaction between this genotype and the CFH SNP rs800292, with carriers of the G allele who also carried at least one T allele of CETP rs3764261 having a significantly increased risk of AMD and PCV.

“Therefore, CETP could be a modifier gene of CFH in the development of neovascular AMD and PCV, indicating interactions among genes in the complement system and lipid metabolism pathways”, the team writes.

Also identified was a mild association between the ATP-binding cassette subfamily G, member 1 (ABCG1) gene and PCV.

CETP facilitates the transfer of triglycerides from very-low-density lipoproteins and low-density lipoproteins to HDL, which is then internalised by the retinal pigment epithelium and excreted back into the circulation via ABCG1 transporters, the researchers explain.

“Therefore, dysfunction of CETP and ABCG1 may cause accumulation of oxidized lipids in the retina”, they add. “Such oxidation products have been shown to initiate inflammation and abnormal angiogenesis, which contribute to the development of neovascular AMD and PCV.”

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